Human apolipoprotein A-I natural variants: molecular mechanisms underlying amyloidogenic propensity
Human apolipoprotein A-I natural variants: molecular mechanisms underlying amyloidogenic propensity
| cic.isFulltext | true | es |
| cic.isPeerReviewed | true | es |
| cic.lugarDesarrollo | Universidad Nacional de La Plata | es |
| cic.version | info:eu-repo/semantics/publishedVersion | es |
| dc.date.accessioned | 2014-12-17T09:24:26Z | |
| dc.date.available | 2014-12-17T09:24:26Z | |
| dc.identifier.uri | https://digital.cic.gba.gob.ar/handle/11746/200 | |
| dc.title | Human apolipoprotein A-I natural variants: molecular mechanisms underlying amyloidogenic propensity | en |
| dc.type | Artículo | es |
| dcterms.abstract | Human apolipoprotein A-I (apoA-I)-derived amyloidosis can present with either wild-type (Wt) protein deposits in atherosclerotic plaques or as a hereditary form in which apoA-I variants deposit causing multiple organ failure. More than 15 single amino acid replacement amyloidogenic apoA-I variants have been described, but the molecular mechanisms involved in amyloid-associated pathology remain largely unknown. Here, we have investigated by fluorescence and biochemical approaches the stabilities and propensities to aggregate of two disease-associated apoA-I variants, apoA-IGly26Arg, associated with polyneuropathy and kidney dysfunction, and apoA-ILys107-0, implicated in amyloidosis in severe atherosclerosis. Results showed that both variants share common structural properties including decreased stability compared to Wt apoA-I and a more flexible structure that gives rise to formation of partially folded states. Interestingly, however, distinct features appear to determine their pathogenic mechanisms. ApoA-ILys107-0 has an increased propensity to aggregate at physiological pH and in a pro-inflammatory microenvironment than Wt apoA-I, whereas apoA-IGly26Arg elicited macrophage activation, thus stimulating local chronic inflammation. Our results strongly suggest that some natural mutations in apoA-I variants elicit protein tendency to aggregate, but in addition the specific interaction of different variants with macrophages may contribute to cellular stress and toxicity in hereditary amyloidosis. | en |
| dcterms.creator.author | Ramella, Nahuel | es |
| dcterms.creator.author | Schinella, Guillermo Raúl | es |
| dcterms.creator.author | Ferreira, Sergio T. | es |
| dcterms.creator.author | Prieto, Eduardo Daniel | es |
| dcterms.creator.author | Vela, María Elena | es |
| dcterms.creator.author | Ríos, José Luis | es |
| dcterms.creator.author | Tricerri, Alejandra | es |
| dcterms.creator.author | Rimoldi, Omar J. | es |
| dcterms.extent | 11 p. | es |
| dcterms.identifier.other | doi:10.1371/journal.pone.0043755 | es |
| dcterms.identifier.url | Documento Completo | es |
| dcterms.isPartOf.issue | vol. 7, no. 8 | es |
| dcterms.isPartOf.series | Plos One | es |
| dcterms.issued | 2012 | |
| dcterms.language | Inglés | es |
| dcterms.license | Attribution 4.0 International (BY 4.0) | es |
| dcterms.relation | Informe Científico de Investigador: Vela, María Elena (2012-2013) | es |
| dcterms.subject | amyloidosis | en |
| dcterms.subject | fluorescense | en |
| dcterms.subject | inflammation | en |
| dcterms.subject | macrophages | en |
| dcterms.subject | neutrophils | en |
| dcterms.subject | oligomers | en |
| dcterms.subject | polymyxins | en |
| dcterms.subject.materia | Ciencias Químicas | es |
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